Bone loss associated with sustained administration of luteinising hormone releasing hormone (LHRH) agonists, such as buserelin, is attributed to estrogen deficiency. However, the possibility that the LHRH agonists themselves may contribute to the pathogenesis of bone thinning, has not been ruled out. The aim of the present study was to determine whether or not oral 17 beta-estradiol (300 micrograms/kg body wt/week) would fully prevent the osteopenic effect of buserelin (25 micrograms/kg body wt/day s.c.) in the rat. Four groups of animals with 45Ca-labelled skeletons were studied for 4 weeks: group 1, placebo controls; group 2, 17 beta-estradiol; group 3, buserelin; group 4, 17 beta-estradiol + buserelin. Buserelin alone lowered blood estradiol concentrations, increased bone resorption and reduced femur and total body calcium and 45Ca values. Total body calcium values (means +/- SD) were: (mg) 3405 +/- 176; 3250 +/- 282; 2813 +/- 133; 3156 +/- 452 in groups 1 to 4, respectively. Significant osteopenia was present only in group 3 (P less than 0.001). These results support the view that buserelin-mediated bone loss is due to estrogen deficiency. They do not indicate that LHRH agonists per se, play any role in causing bone thinning.